Predictive value of angiogenesis-related gene profiling in patients with HER2-negative metastatic breast cancer treated with bevacizumab and weekly paclitaxel

Oncotarget. 2016 Apr 26;7(17):24217-27. doi: 10.18632/oncotarget.8128.

Abstract

Bevacizumab plus weekly paclitaxel improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC), but its use has been questioned due to the absence of a predictive biomarker, lack of benefit in overall survival (OS) and increased toxicity. We examined the baseline tumor angiogenic-related gene expression of 60 patients with mBC with the aim of finding a signature that predicts benefit from this drug.Multivariate analysis by Lasso-penalized Cox regression generated two predictive models: one, named G-model, including 11 genes, and the other one, named GC-model, including 13 genes plus 5 clinical covariates. Both models identified patients with improved PFS (HR (Hazard Ratio) 2.57 and 4.04, respectively) and OS (HR 3.29 and 3.43, respectively). The G-model distinguished low and high risk patients in the first 6 months, whereas the GC-model maintained significance over time.

Keywords: angiogenesis; bevacizumab and weekly paclitaxel; gene expression; metastatic breast carcinoma; predictive.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / secondary
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Humans
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • Paclitaxel / administration & dosage
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Bevacizumab
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel